Evolution of parasite life history traits: myths and reality

Parasitism has evolved independently several times in many different animal lineages. Observations made on distantly related parasites have revealed a variety of adaptations to parasitism, including changes in physiology, morphology, and life history traits. These observations have led parasitologists to formulate general rules about the evolution of parasites, rules that define a common evolutionary path presumably followed by all parasitic organisms. Robert Poulin uses recent evidence to question the generality of these rules and to show that parasite evolution may take different roads. The selective pressures acting on parasites are diverse and may guide their evolution in any direction, just as they have shaped a wide variety of free-living organisms.     

Navigating the boundaries between metabolism and epigenetics in trypanosomes

Epigenetic marks enable cells to acquire new biological features that favor their adaptation to environmental changes. These marks are chemical modifications on chromatin-associated proteins and nucleic acids that lead to changes in the chromatin landscape and may eventually affect gene expression. The chemical tags of these epigenetic marks are comprised of intermediate cellular metabolites. The number of discovered associations between metabolism and epigenetics has increased, revealing how environment influences gene regulation and phenotype diversity. This connection is relevant to all organisms but underappreciated in digenetic parasites, which must adapt to different environments as they progress through their life cycles. This review speculates and proposes associations between epigenetics and metabolism in trypanosomes, which are protozoan parasites that cause human and livestock diseases.     

Bioinformatic tools for DNA methylation and histone modification: A survey

Epigenetic inheritance occurs due to different mechanisms such as chromatin and histone modifications, DNA methylation and processes mediated by non-coding RNAs. It leads to changes in gene expressions and the emergence of new traits in different organisms in many diseases such as cancer. Recent advances in experimental methods led to the identification of epigenetic target sites in various organisms. Computational approaches have enabled us to analyze mass data produced by these methods. Next-generation sequencing (NGS) methods have been broadly used to identify these target sites and their patterns. By using these patterns, the emergence of diseases could be prognosticated. In this study, target site prediction tools for two major epigenetic mechanisms comprising histone modification and DNA methylation are reviewed. Publicly accessible databases are reviewed as well. Some suggestions regarding the state-of-the-art methods and databases have been made, including examining patterns of epigenetic changes that are important in epigenotypes detection.     

Genome Editing by CRISPR/Cas9: A Game Change in the Genetic Manipulation of Protists

Genome editing by CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR‐associated gene 9) system has been transformative in biology. Originally discovered as an adaptive prokaryotic immune system, CRISPR/Cas9 has been repurposed for genome editing in a broad range of model organisms, from yeast to mammalian cells. Protist parasites are unicellular organisms producing important human diseases that affect millions of people around the world. For many of these diseases, such as malaria, Chagas disease, leishmaniasis and cryptosporidiosis, there are no effective treatments or vaccines available. The recent adaptation of the CRISPR/Cas9 technology to several protist models will be playing a key role in the functional study of their proteins, in the characterization of their metabolic pathways, and in the understanding of their biology, and will facilitate the search for new chemotherapeutic targets. In this work we review recent studies where the CRISPR/Cas9 system was adapted to protist parasites, particularly to Apicomplexans and trypanosomatids, emphasizing the different molecular strategies used for genome editing of each organism, as well as their advantages. We also discuss the potential usefulness of this technology in the green alga Chlamydomonas reinhardtii.     

An epi(c)genetic war: Pathogens,cancer and human genome

Cancer is characterized by inter- and intra-tumor heterogeneity and this is also observed in the context of cancers caused by pathogens. Nearly 20% of all cancers are attributable to pathogenic organisms. Pathogenic infections result in deregulation of gene expression both by genetic and epigenetic mechanisms, thereby causing malignant transformation. Another characteristic of pathogen-induced cancers is the occurrence of chronic inflammation due to activation of the innate and adaptive arms of the immune system. This review focuses on the epigenetic changes induced by oncoviruses, parasites, cancer-causing bacteria and ‘endogenous pathogens’ to trigger host cell proliferation indefinitely as well as the inflammation associated with pathogen-induced cancers. The opportunity of targeting components of both pathogen and host epigenetic machinery to limit tumor progression is also discussed.     

Mechanisms predisposing to childhood overgrowth and cancer

Several overgrowth conditions are believed to be associated with elevated risks of cancer, particularly in childhood. Beckwith-Wiedemann syndrome and Sotos syndrome are the most common overgrowth conditions, and both carry increased risks of certain tumors. In recent years, the identification of both the gene causing Sotos syndrome and the epigenetic subgroups underlying Beckwith-Wiedemann syndrome have enabled clarification of the cancer types and risks associated with these conditions. This has revealed striking differences in the cancer phenotypes associated with different molecular abnormalities. Elucidation of the mechanisms underlying cancer in overgrowth syndromes might yield important insights into the molecular basis of childhood tumors.     

Molecular genetic tools in Toxoplasma and Plasmodium: achievements and future needs

The recent awarding of the Nobel prize to Andrew Fire and Craig Mello for the discovery of RNA-interference (RNAi) in plants once more demonstrated the importance of basic science in understanding biological mechanisms. Importantly, this discovery led to the establishment of powerful approaches to study gene function in a wide array of organisms. While a robust RNAi-technology remains elusive in apicomplexan parasites, other molecular genetic technologies have been introduced in recent years. Now, in the post genomic era, the task is to apply these methods to validate and functionally dissect an ever-expanding list of putative vaccine and drug candidates. The ultimate aim of such studies is to transform our knowledge of the genome to the knowledge of the phenome and ultimately new intervention strategies in these important pathogenic organisms. However, substantial limitations remain to the current repertoire of available molecular tools, which limits a comprehensive analysis of these candidates, especially of essential genes. This review summarises the methodologies available for functional gene analysis in apicomplexan parasites and discusses further needs in tool development.     

Novel epigenetic therapeutic strategies and targets in cancer

The critical role of dysregulated epigenetic pathways in cancer genesis, development, and therapy has typically been established as a result of scientific and technical innovations in next generation sequencing. RNA interference, histone modification, DNA methylation and chromatin remodelling are epigenetic processes that control gene expression without causing mutations in the DNA. Although epigenetic abnormalities are thought to be a symptom of cell tumorigenesis and malignant events that impact tumor growth and drug resistance, physicians believe that related processes might be a key therapeutic target for cancer treatment and prevention due to the reversible nature of these processes. A plethora of novel strategies for addressing epigenetics in cancer therapy for immuno-oncological complications are currently available - ranging from basic treatment to epigenetic editing. – and they will be the subject of this comprehensive review. In this review, we cover most of the advancements made in the field of targeting epigenetics with special emphasis on microbiology, plasma science, biophysics, pharmacology, molecular biology, phytochemistry, and nanoscience.     

Old world blowflies in the new world

Human activity, particularly migration and the export of live animals, can provide vehicles for the dispersal of many parasites and their vectors. These movements, often overlooked until too late, provide potential for epidemic outbreaks and can profoundly alter accepted ideas on the geographic distribution and epidemiological status of particular species. In this review, Brian Laurence discusses the recent rapid spread of blowflies into the americas; these conspicious green flies transport a variety of gastro-intestinal pathogens between their favoured environments of latrines and exposed food, and some species are important parasites of flesh wounds, causing cutaneous myiasis.     

Trans-kingdom Cross-Talk: Small RNAs on the Move

This review focuses on the mobility of small RNA (sRNA) molecules from the perspective of trans-kingdom gene silencing. Mobility of sRNA molecules within organisms is a well-known phenomenon, facilitating gene silencing between cells and tissues. sRNA signals are also transmitted between organisms of the same species and of different species. Remarkably, in recent years many examples of RNA-signal exchange have been described to occur between organisms of different kingdoms. These examples are predominantly found in interactions between hosts and their pathogens, parasites, and symbionts. However, they may only represent the tip of the iceberg, since the emerging picture suggests that organisms in biological niches commonly exchange RNA-silencing signals. In this case, we need to take this into account fully to understand how a given biological equilibrium is obtained. Despite many observations of trans-kingdom RNA signal transfer, several mechanistic aspects of these signals remain unknown. Such RNA signal transfer is already being exploited for practical purposes, though. Pathogen genes can be silenced by plant-produced sRNAs designed to affect these genes. This is also known as Host-Induced Genes Silencing (HIGS), and it has the potential to become an important disease-control method in the future.     

Gene manipulation in parasitic helminths

In light of recent growth in available DNA sequence information for a number of parasitic helminths, it is crucial that suitable gene manipulation technologies are developed to facilitate functional genomic studies in these organisms. In this review we discuss recent progress in the development of these technologies in nematode and platyhelminth parasites of medical and veterinary importance. Specifically, the current status of transient transfection, double-stranded RNA interference and antisense RNA as viable techniques for the manipulation of parasitic helminth gene expression is presented. In addition, the potential for the development of stable, or germ-line, transformation methods in these organisms is also discussed.     

Mechanisms of Giardia lamblia differentiation into cysts.

Microbiologists have long been intrigued by the ability of parasitic organisms to adapt to changes in the environment. Since most parasites occupy several niches during their journey between vectors and hosts, they have developed adaptive responses which allow them to survive under adverse conditions. Therefore, the life cycles of protozoan and helminthic parasites are excellent models with which to study numerous mechanisms involved in cell differentiation, such as the regulation of gene expression, signal transduction pathways, and organelle biogenesis. Unfortunately, many of these studies are very difficult because the conditions needed to elicit developmental changes in parasites remain undetermined in most cases. Recently, several interesting findings were reported on the process of differentiation of Giardia lamblia trophozoites into cysts. G. lamblia is a flagellated protozoan that inhabits the upper small intestine of its vertebrate host and is a major cause of enteric disease worldwide. It belongs to the earliest identified lineage among eukaryotes and therefore offers a unique insight into the progression from primitive to more complex eukaryotic cells. The discovery of a specific stimulus that induces trophozoites to differentiate into cysts, the identification and characterization of encystation-specific molecules, the elucidation of novel biochemical pathways, and the development of useful reagents and techniques have made this parasite an excellent model with which to study differentiation in eukaryotic cells. In this review, we summarize the most recent fundings on several aspects of Giardia differentiation and discuss the significance of these findings within the context of current knowledge in the field.     

Microsporidia: emerging advances in understanding the basic biology of these unique organisms

Microsporidia are long-known parasites of a wide variety of invertebrate and vertebrate hosts. The emergence of these obligate intracellular organisms as important opportunistic pathogens during the AIDS pandemic and the discovery of new species in humans renewed interest in this unique group of organisms. This review summarises recent advances in the field of molecular biology of microsporidia which (i) contributed to the understanding of the natural origin of human-infecting microsporidia, (ii) revealed unique genetic features of their dramatically reduced genome and (iii) resulted in the correction of their phylogenetic placement among eukaryotes from primitive protozoans to highly evolved organisms related to fungi. Microsporidia might serve as new intracellular model organisms in the future given that gene transfer systems will be developed.